BACTERIAL PRODUCTS PRIMARILY MEDIATE FIBROBLAST INHIBITION IN BIOMATERIAL INFECTION

Purpose. The stimulation of fibroblast growth is essential for the nor mal healing and tissue integration of biomaterials. The local elevatio n of proinflammatory mediators in infected perigraft fluid (PGF) may i nhibit this growth. We sought to determine whether infected PGF inhibi ted fibroblast growth, and, if so, whether this was primarily dependen t on the biomaterial, bacteria, or host.Methods. In vivo Dacron or exp andable polytetrafluoroethylene (ePTFE) grafts, sterile or colonized w ith slime-producing (RP-62A, viable or formalin-killed) or nonslime-pr oducing (RP-62NA) Staphylococcus epidermidis (1 x 10(7) CFU/cm(2)), we re implanted in Swiss Webster mice, and the PGF was harvested at 7 and 28 days. Antibodies to tumor necrosis factor alpha, interleukin 1 alp ha, interferon gamma (7 gamma g/day), and indomethacin (50 mu g/day) w ere administered by microinfusion pumps for 7 days and the PGF was har vested. Inhibition of the proinflammatory mediators was confirmed by e nzyme-linked immunosorbant assay. The nontreated, heat-treated, or try psin-digested in vivo PGF was incubated with an in vitro [H-3]thymidin e murine fibroblast (ATCC CCL-12) proliferation assay. Results. Fibrob last inhibition was significant at 7 and 28 days with infected PGF inc ubation compared with sterile and was not dependent on bacterial slime production or viability. Dacron sterile PGF did not significantly inh ibit fibroblasts compared with control, whereas sterile ePTFE stimulat ed (P < 0.05) fibroblasts, Treatment of the PGF with proinflammatory c ytokines, heat, and trypsin failed to reverse fibroblast inhibition in the infected state. Conclusion. Biomaterial infection is associated w ith fibroblast inhibition that is dependent primarily on bacterial pro ducts and not the host or biomaterial, Conservative intervention strat egies for graft infection need to address the problem of poor healing as well as bacterial clearance. (C) 1998 Academic Press.